Lung-cancer incidence has been decreasing in part because of a decrease in smoking. However, the decline in population-based mortality from non–small-cell lung cancer has been greater than can be ...accounted for by cancer screening and a decrease in cancer incidence. Evidence indicates that advances in treatment account for the acceleration in decreased mortality.
Toward a Shared Vision for Cancer Genomic Data Grossman, Robert L; Heath, Allison P; Ferretti, Vincent ...
The New England journal of medicine,
09/2016, Volume:
375, Issue:
12
Journal Article
Peer reviewed
Open access
The Genomic Data Commons will initially house raw genomic data and diagnostic, histologic, and clinical outcome data from National Cancer Institute–funded projects. A harmonization process will align ...sequencing data to the genome and identify mutations and alterations.
For the past 2 years, the National Cancer Institute (NCI), the University of Chicago, the Ontario Institute for Cancer Research, and Leidos Biomedical Research have been developing an information system called the NCI Genomic Data Commons (GDC) (see figure). The GDC will initially contain raw genomic data as well as diagnostic, histologic, and clinical outcome data from NCI-funded projects such as the Cancer Genome Atlas (TCGA) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program. Unlike previous versions of these data sets, the genomic data will be “harmonized” using uniform analytic pipelines to align the raw sequencing data . . .
Identification of HPV infection as the etiologic agent of virtually all cases of cervical cancer, as well as a proportion of other epithelial cancers, has led to development of three FDA-approved ...multivalent prophylactic HPV vaccines composed of virus-like particles (VLPs). This essay describes the research and development that led to the VLP vaccines; discusses their safety, efficacy, and short-term effect on HPV-associated disease; and speculates that even a single dose of these vaccines, when given to adolescents, might be able to confer long-term protection. The HPV field exemplifies how long-term funding for basic research has lead to clinical interventions with the long-term potential to eradicate most cancers attributable to HPV infection. Although this essay is the result of my receiving the 2015 Harrington Prize for Innovation in Medicine from the Harrington Discovery Institute and the American Society for Clinical Investigation, this clinical advance has depended on the research of many investigators, development of commercial vaccines by the pharmaceutical companies, and participation of many patient volunteers in the clinical trials.
When it comes to precision oncology, proteogenomics may provide better prospects to the clinical characterization of tumors, help make a more accurate diagnosis of cancer, and improve treatment for ...patients with cancer. This perspective describes the significant contributions of The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium to precision oncology and makes the case that proteogenomics needs to be fully integrated into clinical trials and patient care in order for precision oncology to deliver the right cancer treatment to the right patient at the right dose and at the right time.
Multiomics approaches that collectively integrate proteomics and genomics provide new layers into our understanding of the mechanisms of tumorigenesis across diverse cancer types and patients and provide the path towards treatment through rationalized precision oncology.
The coalescence of new scientific insights and technological innovations has improved our prospects for success against cancer. The cancer “moonshot” aims to increase the resources devoted to ...fighting cancer and break down silos to unite the cancer-fighting community.
“
For the loved ones we’ve all lost, for the families that we can still save, let’s make America the country that cures cancer once and for all
” (President Barack Obama, State of the Union Address, January 12, 2016).
“
We’re talking about prevention and early detection. I’m convinced we can get answers and come up with game-changing treatments and get them to people who need them. We have an opportunity to fundamentally change the trajectory
” (Vice President Joe Biden, University of Pennsylvania Abramson Cancer Center, January 15, 2016).
Cancer is hundreds of diseases. Biomedical research has made . . .
Cell migration requires coordination between integrin-mediated cell adhesion to the extracellular matrix and force applied to adhesion sites. Talin plays a key role in coupling integrin receptors to ...the actomyosin contractile machinery, while deleted in liver cancer 1 (DLC1) is a Rho GAP that binds talin and regulates Rho, and therefore actomyosin contractility. We show that the LD motif of DLC1 forms a helix that binds to the four-helix bundle of the talin R8 domain in a canonical triple-helix arrangement. We demonstrate that the same R8 surface interacts with the paxillin LD1 and LD2 motifs. We identify key charged residues that stabilize the R8 interactions with LD motifs and demonstrate their importance in vitro and in cells. Our results suggest a network of competitive interactions in adhesion complexes that involve LD motifs, and identify mutations that can be used to analyze the biological roles of specific protein-protein interactions in cell migration.
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•The DLC1 LD motif forms a helix that binds the talin R8 rod domain•Talin R8 also binds paxillin LD motifs and recruits paxillin to focal adhesions•Charge complementarity is key to the interaction between LD motifs and talin R8
DLC1 activity depends on binding of its LD motif to talin. Zacharchenko et al. report the structure of the DLC1/talin R8 rod domain complex. They define charge interactions critical for LD-motif recognition by the R8 helical bundle and identify paxillin as a novel talin binding protein.
Approximately, 1.4 million virus-induced cancers occur annually, representing roughly 10% of the worldwide cancer burden, with the majority (> 85%) occurring in the lower- and middle-income ...countries. The viruses associated with the greatest number of cancer cases are human papillomaviruses (HPVs), which cause cervical cancer and several other epithelial malignancies, and hepatitis viruses HBV and HCV, which are responsible for the majority of hepatocellular cancer. Other oncoviruses include Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyoma virus (MCPyV). These oncoviruses include various classes of DNA and RNA viruses and induce cancer by a variety of mechanisms. However, cancers develop in a minority of infected individuals and almost always after chronic infection of many year's duration. Identification of the oncoviruses has provided critical insights in human carcinogenesis and led to several interventions that may reduce the risk of developing the tumors they induce. These interventions include preventive vaccines against HBV and HPV, screening for persistent HPV and HCV infections, antivirals for the treatment of chronic HBV and HCV infection, and screening the blood supply for the presence of HBV and HCV. Further efforts to identify additional oncogenic viruses in human cancers and new insights into etiology and pathogenesis of virally induced cancers would likely lead to new approaches for prophylactic and therapeutic interventions.
Human papillomavirus (HPV) is a necessary cause of cervical cancer. In addition, on the basis of the fulfillment of a combination of viral as well as epidemiological criteria, it is currently ...accepted that a proportion of anal, oropharyngeal, vulvar, and vaginal cancers among women and anal, oropharyngeal, and penile cancers among men are etiologically related to HPV. At these noncervical sites with etiologic heterogeneity, HPV‐associated cancers represent a distinct clinicopathological entity, which is generally characterized by a younger age at onset, basaloid or warty histopathology, association with sexual behavior, and better prognosis, when compared with their HPV‐negative counterparts. Currently available estimates indicate that the number of HPV‐associated noncervical cancers diagnosed annually in the US roughly approximates the number of cervical cancers, with an equal number of noncervical cancers among men and women. Furthermore, whereas the incidence of cervical cancers has been decreasing over time, the incidence of anal and oropharyngeal cancers, for which there are no effective or widely used screening programs, has been increasing in the US. The efficacy of HPV vaccines in preventing infection at sites other than the cervix, vagina, and vulva should, therefore, be assessed (eg, oral and anal). Given that a substantial proportion of cervical cancers (approximately 70%) and an even greater proportion of HPV‐associated noncervical cancers (approximately 86% to 95%) are caused by HPV16 and 18 (HPV types that are targeted by the currently available vaccines), current HPV vaccines may hold great promise (provided equivalent efficacy at all relevant anatomic sites) in reducing the burden of HPV‐associated noncervical cancers, in addition to cervical cancers. Cancer 2008;113:(10 suppl):3036–46. Published 2008 by the American Cancer Society.
An estimated 5% of human cancers are caused by human papillomavirus (HPV) infections, and most of these cancers are of the cervix. Two prophylactic HPV vaccines that target the two most oncogenic ...virus types, HPV16 and HPV18, are now commercially available. In controlled clinical trials, the vaccines proved to be effective at preventing incident anogenital infection and the associated neoplastic disease that is induced by these virus types. Here, we highlight the specific aspects of HPV biology and vaccine composition that are likely to contribute to the efficacy of these vaccines, and we discuss how these particular features might or might not be relevant for the development of effective vaccines against other sexually transmitted viruses such as HIV and herpes simplex virus (HSV).
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